Urinary Stone Disease

1. Dr. Jerry Santos Li, Kingbherly Lichauco, Rafael Lim, Imee Loren Lim, Jason Morven Lim, John Harold Lim, Mary Lim Phoebe Ruth Urinary Stone Disease

2. Polycrystalline aggregates composed of varying amounts of crystalloid and organic matrix • Stone formation requires supersaturated urine • Urinary pH, ionic strength, solute concentration, complexation • Urinary constituents change dramatically during different physiologic states Etiology

3. Greater concentration of 2 ions The more likely they are to precipitate Solubility product (Ksp) = as ion concentrations increase, their activity product reaches a specific point Formation product (Kfp) = concentration above Ksp capable of initiating crystal growth and heterogeneous nucleation Role of solute concentration

4. Urinary stones originate from crystals or foreign bodies immersed in supersaturated urine Nucleation theory CRYSTAL INHIBITOR THEORY • Calculi form owing to absence or low concentration of natural stone inhibitors • Magnesium, citrate, pyrophosphate, trace metals

5. Stones are primarily composed of crystalline component • Crystal formation • Nucleation, growth, aggregation A. Crystal Component

6. Theory of mass precipitation • Distal tubules or collecting ducts becomes plugged with crystals, establishing an environment of stasis, for further stone growth • Tubules enlarge as they entire papilla, transit time is only a few minutes • Fixed particle theory • Formed crystals retained within cells or beneath tubular epithelium

7. Noncrystalline matrix component 2-10% by weight • Mainly protein with hexose and hexosamine • Matrix Calculus • assoc with previous kidney surgery or chronic UTI • Gelatinous texture • May serve as a nidus for crystal aggratation B. Matrix Component

8. Calcium Oxalate Urinary ions • Major ion present in urinary crystals • 95% calcium filtered at glomerulus is reabsorbed at proximal and distal tubules • <2% excreted in urine • Diuretics – hypocalciuric effect, decrease calcium excretion • Normal waste product of metabolism, relatively insoluble • Enters large bowel, consumed by bacterial decomposition • Excreted by proximal tubule • Supersaturation of calcium oxalate • Hyperoxaluria – bowel disorders

9. Phosphate Uric Acid Urinary ions • Important buffer, complexes with calcium in urine • Filtered cy glomerulus, reabsorbed in proximal tubules • Parathyroid hormone inhibits reabsorption • By-product of purine metabolism • Any defect in purine metabolism = urinary stone disease • Defect in xanthine oxidase • Xanthine may ppt in urine

10. Sodium Citrate Urinary ions • Important role in regulating crystallization of calcium salts in urine • High dietary calcium – increases urinary calcium excretion • Reduces ability of urine to inhibit calcium oxalate crystal agglomeration • Pivotal role in citric acid cycle in renal cells • Estrogen increases citrate excretion , factor that decreases incidence of stones in women • Alkalosis increases citrate excretion

11. Magnesium Sulfate Urinary ions • Lack of magnesium is associated with increased calcium oxalate stone formation • Prevent urinary calculi • Complex with calcium

12. Stone Varieties

13. Stone Varieties • Calcium Calculi • Absorptive hypercalciuricnephrolithiasis • Resorptivehypercalciuricnephrolithiasis • Renal induced hypercalciuricnephrolithiasis • Hyperuricosuric Ca nephrolithiasis • Hyperoxaluric Ca nephrolithiasis • Hypocitraturic Ca nephrolithiasis • Non-Calcium Calculi • Struvite or Magnesium Ammonium Phosphate • Uric Acid • Cystine • Xanthine • Indinavir • Rare • Silicate • Triamterene

14. Calcium Calculi • Calcifications accumulate in collecting system  Nephrolithiasis (calcareous) • elevated urinary calcium • elevated urinary uric acid • elevated urinary oxalate • decreased level urinary citrate • Symptoms secondary to obstruction: • Pain • Infection • Nausea • Vomiting • Asymptomatic hematuria or UTI  urinary stone

15. Absorptive HypercalciuricNephrolithiasis

16. Absorptive HypercalciuricNephrolithiasis

17. typically found in hyperparathyroidism • calcium is released from bone in response to the increased activity of osteoclasts caused by excessive and inappropriate serum PTH levels • causes significant hypercalcemia • PTH causes the kidney to limit calcium excretion, but, with the overwhelming serum calcium load produced with hyperparathyroidism, the kidneys are forced to excrete the extra calcium into the urine, causing the hypercalciuria. ResorptiveHypercalciuricNephrolithiasis

18. Renal Induced HypercalciuricNephrolothiasis

19. Excessive purine • Increased uric acid production • Increased urinary monosodium urates • Management: • Diet modification • DOC: allopurinol 300mg/day • Potassium citrate Hyperuricosuric Calcium Nephrolithiasis

20. Hyperoxaluric Calcium Nephrolithiasis

21. Hypocitraturic Calcium Nephrolithiasis

22. Noncalcium Calculi

23. Composed of Magnesium, Ammonium, & Phosphate (MAP) • Most common in women • Frequently present as renal staghorn calculi • Struvite stones are associated with urea-splitting organisms • Proteus • Pseudomonas • Providencia • Klebsiella • Staphylococci • Mycoplasma Struvite

24. Alkaline Urinary pH • Results from the high ammonium concentration derived from the urea-splitting organisms • pH >7.2 (NV: 5.85) • MAP crystals precipitate • MAP crystals are soluble in the normal urinary pH range (5-7) • Foreign bodies and neurogenic bladders may predispose patients to urinary infections and subsequent struvite stone formation

25. Stone removal is therapeutic • Long term management • Optimized with removal of foreign bodies • All stone fragments should be removed with or w/o the aid of follow-up irrigations • Acetohydroxemic acid • Inhibits the action of bacterial urease, thereby reducing the urinary pH and decreasing the likelihood of precipitations

26. <5% of all urinary calculi • Usually found in men • High incidence of Uric Acid Lithiasis • Gout • Myeloproliferative disease • Rapid weight loss • Those treated for malignant conditions with cytotoxic drugs Uric Acid

27. Treatment • Centered on: • Maintaining a urine volume of >2L / dayand a urinary pH of 6 • Reducing dietary purines or the administration of allopurinol helps reduce uric acid excretion • Alkalinization • with oral sodium bicarbonate, potassium citrate, or IV 1/6 normal sodium lactate • May dissolve calculi and is dependent on the stone surface area

28. Secondary to an inborn error of metabolism resulting in abnormal intestinal mucosal absorption and renal tubular absorption of dibasic amino acids • Cystine • Ornithine • Lysine • Arginine Cystine

29. Genetic defects of cystinuria has been mapped to chromosome 2p.16 and 19q13.1 • Cystine lithiasis • Only clinical manifestation of this defect • 1-2% of all urinary stones • Suspected in patients with a (+) FH of urinary stones and the radiographic appearance of a faintly opaque, ground-glass, smooth-edged stone • Urinalysis: hexagonal crystals

30. Medical Therapy • High fluid intake (>3L/day) • Urinary alkalinization • Penicillamine • Reduce urinary cystine levels • Poorly tolerated by some patients (skin rashes, loss of taste, nausea, vomiting, & anorexia) • Mercaptopropionylglycine • Forms soluble complex with cystine and can reduce stone formation • Surgical • Most stones are recalcitrant to ESWL

31. Secondary to a congenital deficiency of xanthine oxidase • Catalyzes the oxidation of hypoxanthine to xanthine and of xanthine to uric acid • Urinary stones develop on 25% of patients with xanthine oxidase deficiency • Stones are radiolucent and are tannish yellow in color Xanthine

32. Treatment • Directed by symptoms and evidence of renal obstruction • High fluid intake • Urinary Alkalinization • Stone recurrence • Trial of Allopurinol • Purine-restricted diet

33. Protease inhibitors are a popular and effective treatment in patients with AIDS • Indinavir • 6% of patients prescribed had radiolucent stones • Indinavir calculi > only urinary stones to be radiolucent on non-contrast CT scans • Associated with calcium components • Stones are tannish red • Temporary cessation of the medication with intravenous hydration frequently allows thes stones to pass Indinavir

34. Silicate • Associated with long term use of antacids containing silica • Surgical treatment • Triamterene • Associated with anti-hypertensive medications containing triamterene (Dyazide) • Discontinuing the medication eliminates stone recurrence • Glafenine • Antrafenine Rare

35. Signs and Symptoms

36. Colicky • Noncolicky • Usually acute in onset, relatively constant, unexpected and severe • Urinary obstruction • due to a direct increase in intraluminalpressure stretching nerve endings • inflammation, edema, hyperperistalsis, and mucosal irritation Pain

37. Affected by: • Stone size • Location • Degree of obstruction • Variation of individual anatomy • Patients frequently move constantly into unusual positions in contrast to the lack of movement of someone with peritoneal signs

38. Renal calyx— deep, dull ache in the flank or back • Mild to severe • Frequently small • may be exacerbated after consumption of large amounts of fluid • the presence of infection or inflammation in the calyx or diverticulum may contribute to pain perception. • occasionally result in spontaneous perforation with urinoma, fistula, or abscess formation

39. Renal pelvis • >1 cm in diameter - obstruct the ureteropelvicjunction • causing severe pain in the costovertebral angle, just lateral to the sacrospinalis muscle and just below the 12th rib • dull to excruciatingly sharp, constant, boring • Radiates along the course of the ureter and into the testicle

40. Partial or complete staghorn calculi- are not necessarily obstructive, few symptoms, “silent” • can often lead to significant morbidity, including renal deterioration, infectious complications, or both

41. Upper and midureter • severe, sharp back (costovertebralangle) or flank pain • progressing down the ureter – more severe and intermittent • lodged at a particular site - less pain, especially if it is only partially obstructive • Upper ureteral- lumbar region and flank

42. Midureteral - radiates caudally and anteriorly toward the mid and lower abdomen in a curved, band-like fashion (initially parallels the lower costal margin but deviates caudal toward the bony pelvis and inguinal ligament)

43. Distal ureter pain that radiates to the groin or testicle in males and the labia majora in females (ilioinguinalor genital branch of the genitofemoral nerves) This pain pattern is likely due to the similar innervation of the intramural ureter and bladder Bladder – urgency and frequency with burning (inflammation of the bladder wall around the ureteral orifice)

44. complete urinalysis : hematuriaand crystalluria and documenting urinary pH intermittent gross hematuria or occasional tea-colored urine (old blood) Rarely (in 10–15% of cases), complete ureteral obstruction presents without microhematuria. Hematuria

45. Magnesium ammonium phosphate (struvite) stones = infection stones • Proteus, Pseudomonas, Providencia, Klebsiella, and Staphylococcus infections • Calcium phosphate stones • urine pH <6.6 - brushite stones • urinary pH >6.6 - infectious apatite stones • All stones, however, may be associated with infections secondary to obstruction and stasis proximal to the offending calculus. • Infection pain • Uropathogenic bacterial exotoxins and endotoxinsmay alter ureteral peristalsis • Local inflammationchemoreceptor activation and perception of local pain Infection

46. Pyonephrosis—gross pus in an obstructed collecting system extreme form of infected hydronephrosis Presentation: may range from asymptomatic bacteriuria to florid urosepsis Renal urine aspiration - definitive diagnosis untreated renocutaneous fistula

47. Evaluation

48. Differential Diagnosis • mimic other retroperitoneal and peritoneal pathologic states • Peritoneal signs should be sought during physical examination • History • onset, character, potential radiation, activities that exacerbate or ease the pain, associated nausea and vomiting or gross hematuria, and a history of similar pain

49. Crystalluria • The rate of stone formation is proportional to the percentage of large crystals and crystal aggregates. • Crystal production is determined by the saturation of each salt and the urinary concentration of inhibitors and promoters. • Urine samples – fresh, centrifuged and examined immediately Risk factors

50. 2. Socioeconomic factors • affluent, industrialized countries 3. Diet • less energy-dense diet may decrease the incidence of stones • Vegetarians may have a decreased incidence of urinary stones. • High sodium intake is associated with increased urinary sodium, calcium, and pH, and a decreased excretion of citrate; • Fluid intake and urine output